Activated form of vitamin D3 (1α,25-dihydroxyvitamin D3, 1,25-(OH)2D3) is known as a metabolic regulatory hormone of calcium and phosphorus, and it exhibits various biological activities such as cellular induced differentiation, suppression of proliferation, and immunomodulation. These activities are expressed by transcription control of target gene mediated by the vitamin D receptor (VDR) that exists in the nucleus. 1,25-(OH)2D3 is applied to treatment of renal osteodystrophy, D-resistant rickets, hypoparathyroidism, osteoporosis, and psoriasis. It is also expected as a candidate of therapeutic agent against cancers and immune diseases. However, administration of effective amounts as therapeutic agent against cancers and immune diseases causes harmful hypercalcemia. Thus, it has been desired to develop vitamin D derivatives that dissociate an increasing activity of serum calcium from a cellular induced differentiation activity. In the study of synthesis of the derivatives have selectivity of cellular induced differentiation activity, attention has been focused mostly on modification of the side chain of the derivatives. However, DeLuca et al. have been prepared the A-ring modified by removing the 19-exomethylene group from 1,25-(OH)2D3, that is, 19-nor-1α,25-dihydroxyvitamin D3 (hereinafter referred to as 19-nor-1,25-(OH)2D3)(Perlman K. L., Swenson R. E., Paaren H. E., Schnoes H. K., DeLuca H. F., Tetrahedron Lett., 1991, 32, 7663-7666.). Comparing the biological activities of 19-nor-1,25-(OH)2D3 with one of the activated 1,25-(OH)2D3, it was shown that VDR affinity was reduced to approximately one-third and the bone resorption activity was reduced to one-tenth or less of 1,25-(OH)2D3, but 19-nor-1,25-(OH)2D3 still retained the cellular effects equivalent to 1,25-(OH)2D3. 19-nor-1,25-(OH)2D3 revealed a selective activity profile with potent cellular differentiation and very low calcium mobilizing activity. In addition, 19-norvitamin D derivatives with a variety of substituents at C-2 position on the A-ring have been synthesized and literature data concerning interesting biological potency of 2-substituted 19-norvitamin D derivatives have been accumulated (Sicinski R. R., Perlman K. L., DeLuca H. F., J. Med. Chem., 1994, 37, 3730-3738; Sicinski R. R., Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 1998, 41, 4662-4674; Sicinski R. R., Rotkiewicz P., Kolinski A., Sicinska W., Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 2002, 45, 3366-3380; Yukiko Iwasaki et al., The 121st Annual Meeting of the Pharmaceutical Society of Japan, Abstract 3, p 17, 29[PB]II-011, 2001 (Sapporo); Akihiro Yoshida et al, The 121st Annual Meeting of the Pharmaceutical Society of Japan, Abstract 3, p 17, 29[PB]II-014, 2001 (Sapporo); Yukiko Iwasaki et al., The 122nd Annual Meeting of the Pharmaceutical Society of Japan, Abstract 3, p 180, 28[P]I-184, 2002 (Chiba); Masato Shimizu et al, The 56th Annual Meeting of the Vitamin Society of Japan, Abstract, Vitamin, 76, 155-156, 2002 (Tokyo); Masato Shimizu et al, 28th Symposium on Progress in Organic Reactions and Syntheses—Applications in the Life Sciences-, Abstract, pp 234-235, 2002 (Tokyo)). Introduction of an alkyl or alkylidene moiety at C-2 position of 19-nor-1,25-(OH)2D3 causes increased activity of serum calcium as well as cellular induced differentiation (Sicinski R. R., Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 1998, 41, 4662-4674; Sicinski R. R., Rotkiewicz P., Kolinski A., Sicinska W., Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 2002, 45, 3366-3380.).
However, in the conventional synthetic studies of 2-substituted 19-norvitamin D derivatives, most of the derivatives have a single substituent at C-2 position. Concerning 20-epi-19-norvitamin D derivatives, 19-norvitamin D derivatives bearing 2-methyl, 2-ethyl or 2-hydroxymethyl moiety have been synthesized so far. (Sicinski R. R., Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 1998, 41, 4662-4674; Sicinski R. R., Rotkiewicz P., Kolinski A., Sicinska W, Prahl J. M., Smith C. M., DeLuca H. F., J. Med. Chem., 2002, 45, 3366-3380.). It has been desired to develop derivatives having more excellent biological activities.